LAUSR

Abstract In the CNS communication between neurons occurs at synapses by secretion of neurotransmitter via exocytosis of synaptic vesicles (SVs) at the active zone. Given the limited number of SVs in presynaptic boutons a fast and efficient recycling of exocytosed membrane and proteins by triggered compensatory endocytosis is required to maintain neurotransmission. Thus, pre-synapses feature a unique tight coupling of exo- and endocytosis in time and space resulting in the reformation of SVs with uniform morphology and well-defined molecular composition. This rapid response requires early stages of endocytosis at the peri-active zone to be well choreographed to ensure reformation of SVs with high fidelity. The pre-synapse can address this challenge by a specialized membrane microcompartment, where a pre-sorted and pre-assembled readily retrievable pool (RRetP) of endocytic membrane patches is formed, consisting of the vesicle cargo, presumably bound within a nucleated Clathrin and adaptor complex. This review considers evidence for the RRetP microcompartment to be the primary organizer of presynaptic triggered compensatory endocytosis.